Conventional T-bet+Foxp3 Th1 cells are the major source of host-protective regulatory IL-10 during intracellular protozoan infection

D Jankovic, MC Kullberg, CG Feng… - The Journal of …, 2007 - rupress.org
D Jankovic, MC Kullberg, CG Feng, RS Goldszmid, CM Collazo, M Wilson, TA Wynn…
The Journal of experimental medicine, 2007rupress.org
Although interferon γ (IFN-γ) secretion is essential for control of most intracellular pathogens,
host survival often also depends on the expression of interleukin 10 (IL-10), a cytokine
known to counteract IFN-γ effector functions. We analyzed the source of regulatory IL-10 in
mice infected with the protozoan parasite Toxoplasma gondii. Unexpectedly, IFN-γ–
secreting T-bet+ Foxp3− T helper type 1 (Th1) cells were found to be the major producers of
IL-10 in these animals. Further analysis revealed that the same IL-10+ IFN-γγ population …
Although interferon γ (IFN-γ) secretion is essential for control of most intracellular pathogens, host survival often also depends on the expression of interleukin 10 (IL-10), a cytokine known to counteract IFN-γ effector functions. We analyzed the source of regulatory IL-10 in mice infected with the protozoan parasite Toxoplasma gondii. Unexpectedly, IFN-γ–secreting T-bet+Foxp3 T helper type 1 (Th1) cells were found to be the major producers of IL-10 in these animals. Further analysis revealed that the same IL-10+IFN-γγ population displayed potent effector function against the parasite while, paradoxically, also inducing profound suppression of IL-12 production by antigen-presenting cells. Although at any given time point only a fraction of the cells appeared to simultaneously produce IL-10 and IFN-γ, IL-10 production could be stimulated in IL-10IFN-γ+ cells by further activation in vitro. In addition, experiments with T. gondii–specific IL-10+IFN-γ+ CD4 clones revealed that although IFN-γ expression is imprinted and triggered with similar kinetics regardless of the state of Th1 cell activation, IL-10 secretion is induced more rapidly from recently activated than from resting cells. These findings indicate that IL-10 production by CD4+ T lymphocytes need not involve a distinct regulatory Th cell subset but can be generated in Th1 cells as part of the effector response to intracellular pathogens.
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